DNA Methylation in Human Breast Cancer Cell Lines Adapted to High Nitric Oxide

Abstract

Background: Nitric oxide (NO) exposure has been suggested to cause alterations in DNA methylation in breast cancer. We investigated the effect of NO on DNA methylation of promoters in cell lines of breast cancer. Material and Methods: The methylation status of the promoters of breast cancer 1 (BRCA1), deleted in colon cancer (DCC), Rasassociation domain family 1A (RASSF1A), O 6-methylguanine-DNA methyltransferase (MGMT), and secreted frizzled related protein 1 (SFRP1) were analyzed in the parental and high nitric oxide-adapted cell lines of breast cancer using Illumina MiSequencing. Results: Methylation of RASSF1A promoter in BT-20-HNO (74.7%) was significantly higher than that in BT-20 cells (72%) (p<0.05), whereas in MCF-7-HNO cells, methylation of MGMT promoter was found to have significantly decreased as compared to its parental cell line (45.1% versus 50.1%; p<0.0001). Promoter methylation of SFRP and DCC was elevated in T-47D-HNO relative to its parent cell line (p<0.05). Conclusion: Similarly to the double-edged effects of NO on tumorigenesis, its epigenetic effects through DNA methylation are diverse and contradictory in breast cancer.

New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way

“…Successively, several array-based studies using different platforms have been performed to analyze the methylation profiles of tissue samples from patients with thyroid cancer [71,72]. These studies highlighted that PTC has one of the lowest frequency of DNA methylation alterations [73], while ATC exhibits a frequency of DNA methylation alterations which was 10 fold that of PTC [74] Nitrate exposition with the consequent NO overproduction could represent of the causes of alterations in methylation levels: NO treatment on cancer cell lines was shown to induce alteration of methylation patterns although the epigenetic effects through DNA methylation were diverse and contradictory in different lines [75]. A recent paper [76] suggested that NO may interfere with methylation patterns by inhibiting the different isoforms of ten-eleven translocation (TET) enzymes, which are responsible of the active removal of methyl group via the catalysis of 5-methylcytosine (5mC) oxidation to 5-hydroxy-(5hmC), 5-formly, and 5-carboxy [77,78].…”